The therapeutic ratio in cancer therapy could be interpreted as the ratio of the effects of an agent or agents on cancer tissue compared to the effects produced in normal tissues. It is desirable to improve the therapeutic ratio with whatever agent or agents are used in the treatment of cancer patients. It is believed that an improvement in the therapeutic ratio may be achieved through an increased knowledge of the cellular and biochemical events occurring in normal and malignant tissue and how they are affected by ionizing radiations, by cancer chemotherapeutic agents, and by possible interactions between these two agents. It is also believed to be desirable to extend this rationale to other aspects of the cancer program such as the immunologic processes involved in tumor growth and metastatic spread. Research programs particularly relevant to this grant supplement are described in a later section of this proposal.